TY - JOUR T1 - Studies on the Mechanism of the L-3,4-Dihydroxyphenylalanine-Induced Decrease in Tyrosine Hydroxylase Activity JF - Molecular Pharmacology JO - Mol Pharmacol SP - 293 LP - 299 VL - 8 IS - 3 AU - WALLACE DAIRMAN AU - SIDNEY UDENFRIEND Y1 - 1972/05/01 UR - http://molpharm.aspetjournals.org/content/8/3/293.abstract N2 - The administration of large amounts of L-3,4-dihydroxyphenylalanine (L-dopa) to rats, guinea pigs, and gerbils decreases the measurable tyrosine hydroxylase activity of adrenal tissues. This effect does not appear to be related to the presence of inhibitory substances in the tissues or a change in the kinetic parameters of the enzyme. The concomitant administration of an aromatic L-amino acid decarboxylase inhibitor, N1-(DL-seryl)-N2-(2,3,4-trihydroxybenzyl)hydrazine (Ro 4-4602), prevents the L-dopa-mediated decrease in tyrosine hydroxylase activity, thus indicating the necessity for decarboxylation of administered L-dopa to catecholamines. The direct involvement of either the endocrine or sympathetic nervous system in this phenomenon is unlikely, since neither hypophysectomy nor adrenal denervation attenutated the L-dopa-induced decrease of adrenal tyrosine hydroxylase activity. ER -